The long term objective of the proposal is to establish the pharmacological rationale for the use of different types of drugs in the treatment of atherosclerotic vascular disease by determining their effects on the pathophysiology and biochemical pathology of experimental atherosclerosis in subhuman primates. The proposed studies are directed toward the development of drug regimens which will arrest and reverse pre-established atherosclerotic vascular disease. The cynomolgus monkey is a valuable model for the investigation of anti-atherosclerotic drugs since the atherosclerotic disease induced in this subhuman primate closely resembles that of humans. On the basis of our prior pharmacological studies we propose to investigate the anti-atherosclerotic effects of two major groups of drugs in the cynomolgus monkey with pre-established atherosclerosis. These include the inhibitors of collagen biosynthesis penicillamine and colchicine and the anticalcifying drugs, dichloro-methyl-diphosphoric acid (Cl2MDP) and p-amino-hexadecyl-benzoic acid (PHB). Their effects on the extent and severity of atherosclerosis will be evaluated at necropsy from the morphological and biochemical findings in the coronary and peripheral arteries. These findings will be correlated with the clinical course of the atherosclerotic disease which will be assessed by plasma lipid and lipoprotein changes, electrocardiogram and measurements of regional myocardial blood flow. In addition the mode of action of the test drugs on the chemical, metabolic and structural changes in the arteries will be investigated with regard to lipids, connective tissue proteins, acid mucopolysaccharides and calcium.